P1206: GASTROINTESTINAL BLEEDING SIGNIFICANTLY REDUCED THE EFFICACY AND SURVIVAL OF CD19 CAR-T CELL THERAPY IN PATIENTS WITH GASTROINTESTINAL TRACT INVOLVEMENT OF REFRACTORY/RELAPSED B-CELL LYMPHOMA
Authors: L. Ma, Y. Dou, R. Liu, T. Xu, F. Yang, F. Xue, P. Zheng, S. Feng, Y. Guo, H. Shi, B. Deng, X. Ke, K. Hu
Journal: HemaSphere (2022)

Background: CD19 Chimeric Antigen Receptor T cell(CAR-T)therapy has been successfully used to treat refractory/relapse B-cell lymphoma (r/r B-NHL). However,the risk was significantly increased due to gastrointestinal bleeding of CAR-T cell therapy for gastrointestinal (GI) lymphoma. Aims: To explored the risk factors of GI bleeding and the efficacy of CAR-T cell therapy for GI lymphoma. Methods: From May 2019 to December 2021,26 patients with r/r B-NHL involvement of the GI tract were enrolled. The male/female ratio was 1.8:1, with a median age of 40.5 years (range, 19-69 years).The diagnosis included diffuse large B-cell lymphoma (DLBCL) (n=21) and Burkitt lymphoma (n=5). All patients were in advanced stage (stage III-IV), and received a median of 7 lines of prior treatment.The disease status was progressive disease (PD)in all patients who failed to multi-line therapies.The median International Prognostic Index (IPI) was 3 (range, 1-4).Most patients (16/26,61.5%) received bridging therapy before CAR T cell infusion.The most common site of involvement was the colonic(10/26,38.5%), followed by small intestinal (8/26,30.8%), gastric (5/26,19.2%) and multiple GI tract sites (3/26, 11.5%).Before the trial, the expression of CD19 antigen in tumor tissue was positive confirmed by pathology. Patients received FC regimen (fludarabine and cyclophosphamide) before CAR-T cells infusion. The kinetics and function of CAR-T cells was monitored by quantitative PCR and flow cytometry. The efficacy was evaluated by PET-CT every 3 month after CAR-T infusion. Results: GI complications occurred in 21/26(80.7%), including GI bleeding in 11/26(42.3%), intestinal obstruction in 2/26 (7.7%), vomiting in and diarrhea in 8/26 (30.8%) respectively.The median GI bleeding time was 4 days(range,1-33days) after CAR-T infusion.The number of patients in bleeding group who received bridging therapy before CAR-T were significantly more than those in non-bleeding group (10/11, 90.9% vs. 6/15, 40%) (P=0.0259). The proportion of patients with ECOG score greater than 3 in bleeding group before CAR-T therapy was significantly higher than that in non-bleeding group (6/11,54.5% vs 2/15, 13.3%)(P=0.0384).There was no significant difference between dose of CAR-T cell infusion (P=1.0) and the median peak lever of CAR-T cells in vivo (P=0.8565) in two groups.The incidence of cytokine release syndrome(CRS)was 84.6%(22/26), of which 27.3%(6/22) was severe CRS (≥grade3).The incidence of ≥grade 3 CRS in GI bleeding group was higher than that in non-bleeding group (5/11, 45.5% vs 1/15, 6.7%) (P=0.0538). Altogether,the best overall response rate (ORR) and complete response rate (CR) rate were 61.5%(16/26) and 26.9%(7/26),respectively.The ORR of GI bleeding group was significantly lower than that of non-bleeding group (3/11,27.3% vs 13/15,86.7%) (P = 0.0076)).With the median follow-up time was 5.8 months (range, 0.5-30.4months), the overall survival(OS) and progression free survival(PFS) in one year were also 50%. OS and PFS rate at 1 year after infusion in GI bleeding group were significantly lower than those in non-bleeding group (OS 27.3% vs 57% (P = 0.0198), PFS 27.3% vs 60.9% (P = 0.0293)).3 cases(3/26,11.5%) died of GI bleeding and 10 cases (10/26,38.4%) died of disease progression. Summary/Conclusion: Our study showed promising efficacy of CAR-T cell therapy in r/r B-NHL involving the GI tract.However the GI bleeding significantly reduced the efficacy and survival.ECOG score greater than 3 and receiving bridging therapy before CAR-T may be the risk factors of GI bleeding.